Magnetically responsive particles (“MRP”) can be useful in biological techniques requiring the separation of a target substance from a sample. As such, the MRP can include moieties that interact or bind with the target substance so that it can be separated from the sample. Typically, MRPs have micro-scale dimensions, and can be useful in immunoassays, for the separation of cells from cell cultures or other samples, and as magnetic resonance imaging agents. Various uses of MRPs have been described in U.S. Pat. Nos. 4,177,253, 4,230,685, 4,329,241, 4,695,392, 4,770,183, 5,069,216, 5,091,206, 5,648,124, 6,133,047, and 6,682,660, which are incorporated herein by reference.
In some instances, it may be preferable for the MRPs to have dimensions (e.g., diameters for spheres), which cover the range of the visible light spectrum so as to facilitate heterogeneous and homogeneous immunoassay methods. However, it can be difficult to prepare a single particle size and associated particle size distribution that can be useful for a broad range of experimental procedures. For example, particles that are useful in automated experimental protocols may not be useful in experiments run by hand.
In some instances, it can be preferable that the MRPs have negligible residual magnetism. Unfortunately, some MRPs having large amounts of MRMs have shown considerable residual magnetism due to the characteristics of the magnetic materials. Such residual magnetism can cause clumping in the absence of a magnetic field in a manner resulting in the magnetic particles being caused to fall out of Brownian motion and quickly settle out of suspension. Further, the large size of magnetite particles that have been used in some MRPs can limit the overall size of the MRP.
Additional problems that can be encountered with MRPs can include the stability and response time of the particle. Usually, increases in particle stability can be offset by longer and unfavorable response times. In part, this is because an increase in materials that are not magnetically responsive imparts particle stability, and addition of such materials can significantly alter the behavior of the particles in solution and/or under a magnetic field. On the other hand, increases in materials that are responsive to magnetic fields can lead to particle instability. It is thought that this may inherently result from the magnetically responsive materials (“MRM”) having adverse reactions with each other as the amount or concentration increases. Also, increasing the amount or concentration of MRMs on a core particle may result in ineffective agglutination leading to instability at the core-MRM boundary, which significantly decreases the lifespan of the particle.
Therefore, it would be advantageous to have an improved MRP that can be used in a broad range of experimental protocols such as in automated and/or manual immunoassays, separation of cells, and magnetic resonance imaging. Additionally, it would be beneficial to have micro-scale MRPs that have improved response times and stability.